Project Summary/Abstract My group seeks to understand molecular mechanisms that underlie the ability of bacterial cells to survive in complex, dynamic environments, including mammalian hosts. In the context of this project, we will specifically focus on defining mechanisms by which bacteria (i) regulate their physiology to survive environmental stress, and (ii) regulate and modify their envelope to control adhesion to surfaces and to other cells. We will utilize an interdisciplinary set of genetic, biochemical, biophysical, and computational approaches to address these questions on multiple scales, from the cellular/systems level to the level of molecular structure. The data that emerge from our studies will enhance understanding of processes that allow bacteria to grow and survive in complex environments, and will inform new concepts in gene regulation and cell envelope biology. More specifically, this project will provide the scientific community with an integrative understanding of sensory transduction mechanisms, from signal detection to cellular response. In addition, our investigations of bacterial cell adhesion and envelope polysaccharide biosynthesis will lead to improved understanding of the molecular mechanisms by which bacteria build the highly complex structure known as the envelope, which separates the tightly controlled activities in the cytoplasm from the outside world. Importantly, both environmental regulatory proteins and components of the bacterial cell envelope are well-defined virulence determinants in many bacterial pathogens. Thus our work has the potential to inform new therapeutic routes to control certain bacterial infections.